Remarkable residual alterations in responses to feeding regulatory challenges in Han/Wistar rats after recovery from the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
Adult male Han/Wistar rats were treated with 1000 micrograms 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg body weight and allowed to restabilize their body weight at a lower level. Therefore, their feeding or drinking responses were determined to the following ip challenges: NaCl (1 M, 10 ml/kg body weight); 2-deoxy-D-glucose (2DG; 400 mg/kg); sodium mercaptoacetate (MA; 800 mumol/kg); 2DG + MA (200 mg/kg + 400 mumol/kg); insulin (10 U/kg). In addition, the suppressive effects of naloxone (10 mg/kg), glucose (1.36 mg/kg) and fructose (1.36 mg/kg) on feed intake stimulated by 24-hr food deprivation were examined. After the restabilization, the body weights of TCDD-treated rats followed the course of body changes in control rats. The responses to NaCl were also similar in TCDD-treated and control rats. However, marked differences were observed in all other responses studied. Pretreatment with TCDD abolished 2DG-induced feeding, attenuated the effects of insulin and naloxone, caused an aberrant decrease in feed intake following MA, and resulted in hypersensitivity to the satiating effects of glucose and fructose. These data show that exposure to a high dose of TCDD leads to notable distortions in responses to metabolic challenges in Han/Wistar rats, which are present even when they have seemingly recovered from the acute toxicity. The results also indicate that the central nervous system plays a crucial role in TCDD toxicity, and suggest hypersensitivity to peripheral satiety signals coupled with hyporesponsiveness to metabolic cues of energy deficit to be important mechanisms in the pathogenesis of the wasting syndrome.
Pohjanvirta
R
R
National Public Health Institute, Department of Environmental Hygiene and Toxicology, Kuopio, Finland.
Tuomisto
J
J
D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D003847:Deoxyglucose / Q000633:toxicity; D004326:Drinking / Q000187:drug effects; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects*; D005508:Food Deprivation; D005632:Fructose / Q000633:toxicity; D005947:Glucose / Q000633:toxicity; D007328:Insulin / Q000633:toxicity; D008297:Male; D009270:Naloxone / Q000633:toxicity; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000633:toxicity; D013864:Thioglycolates / Q000633:toxicity
D007328:Insulin; D000072317:Polychlorinated Dibenzodioxins; D013864:Thioglycolates; D005632:Fructose; D009270:Naloxone; D012965:Sodium Chloride; C017487:2-mercaptoacetate; D003847:Deoxyglucose; D005947:Glucose